scholarly journals Selenoproteins and their emerging roles in signaling pathways

2020 ◽  
Vol 11 (2) ◽  
pp. 186-199
Author(s):  
N. V. Stanishevska
Keyword(s):  
Endoplasmic Reticulum ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Thioredoxin Reductase ◽  
Methionine Sulfoxide ◽  
Mapk Signaling ◽  
Methionine Sulfoxide Reductase ◽  
Selenoprotein S ◽  
Selenoprotein K ◽  
Er Membrane

The functional activity of selenoproteins has a wide range of effects on complex pathogenetic processes, including teratogenesis, immuno-inflammatory, neurodegenerative. Being active participants and promoters of many signaling pathways, selenoproteins support the lively interest of a wide scientific community. This review is devoted to the analysis of recent data describing the participation of selenoproteins in various molecular interactions mediating important signaling pathways. Data processing was carried out by the method of complex analysis. For convenience, all selenoproteins were divided into groups depending on their location and function. Among the group of selenoproteins of the ER membrane, selenoprotein N affects the absorption of Ca2+ by the endoplasmic reticulum mediated by oxidoreductin (ERO1), a key player in the CHOP/ERO1 branch, a pathogenic mechanism that causes myopathy. Another selenoprotein of the ER membrane selenoprotein K binding to the DHHC6 protein affects the IP3R receptor that regulates Ca2+ flux. Selenoprotein K is able to affect another protein of the endoplasmic reticulum CHERP, also appearing in Ca2+ transport. Selenoprotein S, associated with the lumen of ER, is able to influence the VCP protein, which ensures the incorporation of selenoprotein K into the ER membrane. Selenoprotein M, as an ER lumen protein, affects the phosphorylation of STAT3 by leptin, which confirms that Sel M is a positive regulator of leptin signaling. Selenoprotein S also related to luminal selenoproteins ER is a modulator of the IRE1α-sXBP1 signaling pathway. Nuclear selenoprotein H will directly affect the suppressor of malignant tumours, p53 protein, the activation of which increases with Sel H deficiency. The same selenoprotein is involved in redox regulation. Among the cytoplasmic selenoproteins, abundant investigations are devoted to SelP, which affects the PI3K/Akt/Erk signaling pathway during ischemia/reperfusion, is transported into the myoblasts through the plasmalemma after binding to the apoER2 receptor, and into the neurons to the megaline receptor and in general, selenoprotein P plays the role of a pool that stores the necessary trace element and releases it, if necessary, for vital selenoproteins. The thioredoxin reductase family plays a key role in the invasion and metastasis of salivary adenoid cystic carcinoma through the influence on the TGF-β-Akt/GSK-3β pathway during epithelial-mesenchymal transition. The deletion of thioredoxin reductase 1 affects the levels of messengers of the Wnt/β-catenin signaling pathway. No less studied is the glutathione peroxidase group, of which GPX3 is able to inhibit signaling in the Wnt/β-catenin pathway and thereby inhibit thyroid metastasis, as well as suppress protein levels in the PI3K/Akt/c-fos pathway. A key observation is that in cases of carcinogenesis, a decrease in GPX3 and its hypermethylation are almost always found. Among deiodinases, deiodinase 3 acts as a promoter of the oncogenes BRAF, MEK or p38, while stimulating a decrease in the expression of cyclin D1. The dependence of the level of deiodinase 3 on the Hedgehog (SHH) signaling pathway is also noted. Methionine sulfoxide reductase A can compete for the uptake of ubiquitin, reduce p38, JNK and ERK promoters of the MAPK signaling pathway; methionine sulfoxide reductase B1 suppresses MAPK signaling messengers, and also increases PARP and caspase 3.

scholarly journals Targeting ERK-Hippo Interplay in Cancer Therapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3236 ◽  
Author(s):  
Karel Vališ ◽  
Petr Novák
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

Methionine sulfoxide reductase B3 protects from endoplasmic reticulum stress in Drosophila and in mammalian cells

2012 ◽  
Vol 420 (1) ◽  
pp. 130-135 ◽  
Author(s):  
Geun-Hee Kwak ◽  
Do-Hwan Lim ◽  
Jee Yun Han ◽  
Young Sik Lee ◽  
Hwa-Young Kim
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Mammalian Cells ◽  
Methionine Sulfoxide ◽  
Methionine Sulfoxide Reductase

Fisetin induces apoptosis and endoplasmic reticulum stress in human non-small cell lung cancer through inhibition of the MAPK signaling pathway

Tumor Biology ◽  
2016 ◽  
Vol 37 (7) ◽  
pp. 9615-9624 ◽  
Author(s):  
Kyoung Ah Kang ◽  
Mei Jing Piao ◽  
Susara Ruwan Kumara Madduma Hewage ◽  
Yea Seong Ryu ◽  
Min Chang Oh ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Small Cell Lung Cancer ◽  
Signaling Pathway ◽  
Cell Lung Cancer ◽  
Mapk Signaling ◽  
Small Cell ◽  
Mapk Signaling Pathway ◽  
Small Cell Lung

scholarly journals Redox-mediated regulation of a labile, evolutionarily conserved cross-β structure formed by the TDP43 low complexity domain

2019 ◽  
Author(s):  
Yi Lin ◽  
Xiaoming Zhou ◽  
Masato Kato ◽  
Daifei Liu ◽  
Sina Ghaemmaghami ◽  
...  
Keyword(s):  
Rna Binding ◽  
Thioredoxin Reductase ◽  
Methionine Sulfoxide ◽  
Low Complexity ◽  
Methionine Sulfoxide Reductase ◽  
Methionine Residue ◽  
Low Concentrations ◽  
Evolutionarily Conserved ◽  
Methionine Residues ◽  
Self Association

SummaryAn evolutionarily conserved low complexity (LC) domain is found within a 152 residue segment localized to the carboxyl-terminal region of the TDP43 RNA-binding protein. This TDP43 LC domain contains ten conserved methionine residues. Self-association of this domain leads to the formation of liquid-like droplets composed of labile, cross-β polymers. Exposure of polymers to low concentrations of H2O2 leads to a phenomenon of droplet melting that can be reversed upon exposure of the oxidized protein to the MsrA and MsrB methionine sulfoxide reductase enzymes, thioredoxin, thioredoxin reductase and NADPH. Morphological features of the cross-β polymers were revealed by a method of H2O2-mediated footprinting. Similar TDP43 LC domain footprints were observed in highly polymerized, hydrogel samples, liquid-like droplet samples, and living cells. The ability of H2O2 to impede cross-β polymerization was abrogated by a prominent ALS-causing mutation that changes methionine residue 337 to valine. These observations offer potentially useful insight into the biological role of TDP43 in facilitating synapse-localized translation, as well as aberrant aggregation of the protein in neurodegenerative disease.

scholarly journals Proteins in cord blood as a new target for prevention and treatment of bronchopulmonary dysplasia: a proteomic analysis

2021 ◽  
Author(s):  
Juan Wang ◽  
Jianping Mao ◽  
Gang Chen ◽  
Yuanmei Huang ◽  
Jinjin Zhou ◽  
...  
Keyword(s):  
Cord Blood ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Bronchopulmonary Dysplasia ◽  
Proteomic Analysis ◽  
Mapk Signaling ◽  
Term Infants ◽  
Reproductive Process ◽  
Prevention And Treatment ◽  
Differential Proteins

Abstract This study aimed to explore the proteins in cord blood that could regulate the development of neonatal bronchi and lungs, and to find a new target for the prevention and treatment of bronchopulmonary dysplasia (BPD). In this study, proteomic analysis was used to analyze the proteins in cord blood of preterm and term infants. A total of 100 differentially expressed (57 up-regulated and 43 down-regulated) proteins were identified from preterm with BPD and term infants cord blood (fold change ≥ 1.5, P value < 0.05). GO analysis revealed that the major enrichment functions of these differential proteins were multi-organism process, stimulus, immune system process growth, reproductive process, development process and antioxidant activity. The signaling pathways involved included insulin resistance, insulin signaling pathway, IL−17 signaling pathway, PI3K−Akt signaling pathway, NF−kappa B signaling pathway, glucagon signaling pathway, apoptosis, MAPK signaling pathway, as well as glycolysis/gluconeogenesis. Further protein and protein interact (PPI) analysis revealed that the interacting proteins involved were PGAM1, CNN2, HSP90AA and DAG1, which were all crucial in the development of BPD. We found that these differential proteins in cord blood might regulate bronchopulmonary development through the abovementioned signaling pathways or their interaction proteins, which may provide a new research direction for the intervention of BPD.

scholarly journals Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengde Zhao ◽  
Qining Fu ◽  
Liangzhu Hu ◽  
Yangdong Liu
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intimal Hyperplasia ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Biological Processes ◽  
Hub Genes ◽  
Av Fistula ◽  
Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

Cross-talk of Signaling Pathways in the Pathogenesis of Allergic Asthma and Cataract

2020 ◽  
Vol 27 (9) ◽  
pp. 810-822
Author(s):  
Yang Zhao ◽  
Sumei Liu ◽  
Xiangsheng Li ◽  
Zhenzhen Xu ◽  
Lifang Hao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Allergic Asthma ◽  
Signaling Pathway ◽  
Academic Research ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Chronic Inflammatory Disease ◽  
Smad Signaling Pathway ◽  
Immune Imbalance ◽  
Cellular Components

: Allergic asthma is a chronic inflammatory disease, which involves many cellular and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. Both of them belong to diseases induced by immune disorders or inflammation. We want to confirm the signaling pathways involved in the regulation of asthma and cataract simultaneously, and provide reference for the later related experiments. So we conducted a scoping review of many databases and searched for studies (Academic research published in Wiley, Springer and Bentham from 2000 to 2019) about the possible relationship between asthma and cataract. It was found that during the onset of asthma and cataract, Rho/Rock signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, PI3K/AKT signaling pathway, JAK/STAT signaling pathway, MAPK signaling pathway, TGF-β1/Smad signaling pathway and NF-κB signaling pathway are all active, so they may have a certain correlation in pathogenesis. Asthma may be associated with cataract through the eight signaling pathways, causing inflammation or immune imbalance based on allergy that can lead to cataract. According to these studies, we speculated that the three most likely signaling pathways are PI3K/AKT, MAPK and NF-κB signaling pathway.

Malvidin and its derivatives exhibit antioxidant properties by inhibiting MAPK signaling pathways to reduce endoplasmic reticulum stress in ARPE-19 cells

2021 ◽  
Author(s):  
Xinyao Liu ◽  
Fei Zheng ◽  
Sheng Li ◽  
Zhitong Wang ◽  
Xinyuan Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Signaling Pathways ◽  
Molecular Mechanism ◽  
Antioxidant Properties ◽  
Mapk Signaling ◽  
Mapk Signaling Pathways

Diagram of the molecular mechanism of MV, Mv3C, and Mv3ACEC protecting ARPE-19 cells against oxidative stress.

Sign in / Sign up

Export Citation Format

Share Document